PROJECT SUMMARY/ABSTRACT: Smoking is an appetitive behavior and stimuli associated with nicotine?s desirable effects have been shown to increase smoking urge and behavior. As electronic nicotine delivery systems (ENDS, electronic cigarettes, or e-cigarettes) share salient features of traditional smoking in form and function, it is possible they could generalize as a conditioned cue to elicit smoking urge and behavior. This is of critical importance as the availability and rapid adoption of ENDS has led to increased second-hand exposures to vaping that occur in similar contexts as smoking. Thus, even one occasion of e-cigarette use could conceivably result in numerous ENDS products have rapidly evolved with increased popularity for tank systems with variable-voltage/wattage settings. These devices are used in conjunction with e-liquids that include various chemical constituents, including the primary humectant vegetable glycerin (VG). E-liquids with high levels of VG are desirable for both the throat hit as well as their ability to increase exhaled aerosol (vape) production which may affect their cue salience exposures to observers. . Well-controlled, evidence-based research is needed to elucidate the role of e-liquid constituents of ENDS and their aerosols that may affect tobacco use in observers. We propose the first large-scaled controlled study to address this issue. We will examine current and former smokers? cue reactivity to the use of a tank-based ENDS device with different VG content e-liquids. Study 1 will compare subjective and behavioral responses to the use of ENDS with high vs. low VG e-liquids, relative to both a non- smoking control cue (bottled water) and a cigarette cue (active comparison) in a diverse sample of adult daily and nondaily smokers (N=320, 80/cue condition). Study 2 will examine subjective responses to the high VG e- liquid ENDS cue compared to the control and active comparison cues in a sample of former smokers (N=240, 80/cue condition). Smoking behavior and cigarette reinforcement tasks will not be assessed in Study 2 for ethical reasons as participants are not currently smokers. Cue exposures will be delivered via a trained confederate engaging in product use in the presence of the participant. Thus, this paradigm mimics real-world exposures for ecological validity while retaining standardized cue delivery, hand to mouth movements, and interaction quality . The main dependent variables will be cigarette and e-cigarette desire, smoking urge, and smoking behavior (latency to smoke, smoking choice), as well as secondary outcomes including affect, cigarette reinforcement and attentional bias. The results will contribute to our scientific knowledge on the effects of ENDS in terms of the downstream effects of product use. The proposed studies will play a critical role in determining the role of e-liquid constituents that may factor into the ongoing debate about the ENDS? potential benefit versus harm. Second-hand exposures to these devices and the salience of their exhaled aerosols may be an important part of the equation in evaluating the overall effects of ENDS use in society.